1. Field of the Invention
The present invention relates to devices which interface between liquid or supercritical fluid chromatographic units and gas phase or solid phase detectors and, more particularly, relates to an improved interface which transports the sample as an aerosol while efficiently removing most of the solvent vapors.
2. Description of the Prior Art
The detection of effluent from chromatographic devices has been applied to almost all areas of science requiring chemical analysis. Such detectors usually involve the measurement of either (1) a bulk property of the effluent (such as the refractive index) which is sensitive to the presence of the sample, (2) a property of the sample not possessed by the mobile phase (such as optical density at a suitable wavelength), or (3) a property of the sample after elimination of the mobile phase.
In liquid chromatography (LC), the properties of the sample in the mobile phases are often similar to those of the mobile phase itself. An almost universal LC detector comparable to flame ionization for gas chromotography (GC) does not currently exist. Accordingly, reliable detection of LC samples has generally been obtained using equipment specially designed for limited purposes. While LC is applicable to a much broader range of samples than GC, its limited utility is thus partially attributable to the lack of a suitable universal LC detector.
Packed and capillary supercritical fluid chromatography (SFC) are complementary to GC and LC for the analysis of organic compounds. Packed column SFC allows faster analysis and method development, whereas capillary SFC provides better chromatographic efficiency and allows the use of GC detectors. SFC typically uses a relatively nonpolar gas, such as carbon dioxide operated at a high pressure above the critical point. The addition of more polar modifiers, such as methanol, allows SFC to be applied to a wide range of compounds not amenable to GC. When capillary columns are used with pure carbon dioxide as the mobile phase, SFC can be directly coupled to GC detectors with little difficulty. However at the higher flow rates used with packed columns and the addition of polar modifiers, the same kinds of problems common to an LC interface are encountered in coupling SFC to gas phase detectors.
The thermospray technique was developed primarily for coupling liquid chromatography to a particular gas phase detector, namely mass speotrometry. Thermospray technology provides an LC to mass spectrometry interface which has significant advantages compared to other coupling techniques. In thermospray technology, the LC effluent is partially vaporized and nebulized in a heated vaporizer probe to produce a supersonic jet of vapor containing a mist of fine droplets or particles. As the droplets or particles travel at a high velocity through the heated ion source, they continue to vaporize due to rapid heat input from the surrounding hot vapor. Thermospray thus employs controlled heating of the capillary and the ion source to convert the LC liquid stream into gas phase ions for introduction into the mass spectrometer. A more detailed description of the major components and function of the thermospray system are disclosed in U.S. Pat. No. 4,730,111.
A significant disadvantage of thermospray, as well as other direct coupling techniques between liquid chromatographic devices and mass spectrometers, is that ionization occurs in a bath of solvent vapor at a relatively high source pressure (typically 1 torr or more). This pressure effectively precludes the use of electron impact (EI) ionization, and also limits the choice of reagents in chemical ionization (CI). Moreover, detection utilizing thermospray interface technology has heretofore been limited to a fairly narrow range of chromatographic conditions, since thermospray ionization performs best when the solvent flow rate is in excess of 1 mL/minute, and at least 20% of the mobile phase is water.
Various attempts have been made to overcome the limitations of interfaoes between liquid chromatographic units and detectors. One commercially successful technique is similar to that described in U.S. Pat. No. 4,055,987. This technique unfortunately involves various moving wires and belts, and accordingly has significant operational drawbacks which have become widely recognized by those skilled in the art.
A second type of liquid chromatography to gas phase detector interface is known by the acronym MAGIC, which stands for Monodisperse Aerosol Generation Interface for Chromatography. In this device, the LC effluent is forced under pressure through a relatively small orifice (typically 5 to 10 microns in diameter, such that the liquid jet breaks up into a stream of relatively uniform droplets as a result of Rayleigh instability. A short distance downstream, the stream of particles is intersected at 90.degree. by a high velocity gas stream (usually helium) to disperse the particles and prevent coagulation. The dispersed droplets proceed at a relatively high velocity through a desolvation chamber, where vaporization occurs at atmospheric pressure and near ambient temperature. Heating is input to the desolvation chamber to replace the latent heat of vaporization necessary for solvent evaporation, while not raising the aerosol temperature above ambient. Ideally all the solvent is vaporized, and the sample remains as a solid particle or a less volatile liquid droplet. Further details regarding the MAGIC approach are disclosed in an article by Willoughby and Browner published in 1984 in ANALYTICAL CHEMISTRY, Vol. 56, commencing at page 2626, and in U.S. Pat. No. 4,629,478.
A modified version of a particle beam interface between liquid chromatography and mass spectrometry is disclosed in a series of recently published articles. This technique, referred to as Thermabeam LC/MS, uses a nebulizer which may be similar to a thermospray vaporizer. The interface includes a nebulization stage, an expansion stage, and a momentum separation stage, each axially connected in series. In both the MAGIC and the Thermabeam LC/MS devices, some of the carrier gas and some of the solvent vapor is removed in the momentum separator, but no carrier gas or solvent vapor is removed from the desolvation chamber.
While both the second and third types of interfaces described above apparently produce EI spectra in good agreement with library spectra using sample injections of 100 ng or more, these spectra do not include the low mass region where solvent interference may be expected. Accordingly, it is difficult to determine or evaluate the solvent removal efficiency actually achieved by these techniques. Moreover, improved techniques are required to improve sensitivity for gas phase detectors supplied with effluent from LC and HPLC equipment, and to enable the detectors to be utilized over a broader range of chromatographic conditions. Finally, an improved interface is required which will allow LC effluent to be transmitted for analysis to various types of gas phase detectors, so that the flexibility and versatility of the interface is enhanced and its costs minimized.
The disadvantages of the prior art are overcome by the present invention, and improved methods and apparatus are hereinafter disclosed which provide an interface for coupling liquid chromatography or supercritical fluid chromatography to various types of gas phase detectors.